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While a number of potent antibiotics exist for the treatment of bacterial infections, there are very few safe but effective drugs to stave off fungal infections. Many companies -- from large pharmaceuticals to small biotechs -- are racing to be the first to fill the antifungal pipeline. Researchers from Merck, Fujisawa, and Versicor presented exciting results about their new antifungal compounds at the 40th Interscience Conference on Antimicrobial Agents & Chemotherapy in Toronto.
NO LONGER RARE. Human fungal infections, like bacterial infections, can be life-threatening. Experts estimate that the fungus called candida kills 38% of the victims it infects, while another fungus, aspergillus, kills 95% of the time. Such infections were once considered rare but -- with the rise in AIDS cases and other conditions that decimate the immune system -- are becoming more and more common. In 1999, for example, approximately 25% of the 2.5 million patients hospitalized for chemotherapy, organ transplantation, or AIDS developed serious fungus infections. Analysts believe the current market for antifungals to be a huge $2.5 billion and growing.
The current antifungal arsenal is limited to compounds called azoles that inhibit cell growth but don't actually kill the fungus. The idea is that by slowing fungal spread, the body's immune system has more time to get the infection under control. But funguses often become resistant to azoles with prolonged use. Moreover, for unknown reasons, dozens of fungus types simply don't respond to azoles.
INHIBITING CELLS. In an effort to develop new antifungals, scientists are boning up on previous research on antibacterials. Some of the most potent antibacterial drugs in existence target a process called cell-wall synthesis. These so-called cell-wall inhibitors, which include penicillin and next-generation drugs such as Bactrim and Vancomycin, block a critical pathway in the germ's life cycle: how it grows and divides. What if researchers targeted the same steps in the fungal life cycle? Could they stop these nasty infections simply by designing compounds that block fungal growth?
The answer is yes. Research on many fronts has led to the first new class of antifungals in 40 years, the so-called echinocandins. Leading the way is Merck, which recently wrapped up testing in humans of its most potent drug in this class, Cancidas. The company expects to submit its findings on Cancidas to the U.S. Food & Drug Administration before the end of the year. Approval could come as early as 2001. James Kelly, an analyst at Credit Suisse First Boston, sees potential for a $500 million market for Cancidas.
Not too far behind are Fujisawa's FK-463 and Versicor's V-Echinocandin, both in late-stage clinical trials. Kelly expects both compounds to be serious competitors in the next 12 to 24 months, and the market potential for FK-463 to be at least $150 million.
100% CURE RATE? Versicor's compound, VEC, is particularly intriguing to researchers. In a study of patients with esophageal fungal infections, Versicor scientists found that a low dose of VEC wiped out infections of candida 85% of the time. Results of a separate study indicated that a higher dose was safe and had no serious side effects. The company is now measuring VEC's effectiveness at this higher dose to see if it can improve the patients' response rate to nearly 100%.
The echinocandins aren't likely to be panaceas. Over time, bacteria often develop resistance to antibiotics, and the same is likely to be true of echinocandins. Still, for the millions of patients with life-threatening fungal infections, these drugs are the most potent therapy currently available.
By Ellen Licking at the ICAAC in Toronto Edited by Doug Harbrecht
Copyright 2000, by The McGraw-Hill Companies Inc. All rights reserved.
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